College of Arts and Sciences, American University of Sharjah, University City, Sharjah, United Arab Emirates.
Department of Medical Biology, Faculty of Medicine, Istinye University, Istanbul, 34010, Turkey.
Arch Microbiol. 2023 Apr 5;205(5):170. doi: 10.1007/s00203-023-03518-8.
Balamuthia mandrillaris and Naegleria fowleri are protist pathogens that can cause fatal infections. Despite mortality rate of > 90%, there is no effective therapy. Treatment remains problematic involving repurposed drugs, e.g., azoles, amphotericin B and miltefosine but requires early diagnosis. In addition to drug discovery, modifying existing drugs using nanotechnology offers promise in the development of therapeutic interventions against these parasitic infections. Herein, various drugs conjugated with nanoparticles were developed and evaluated for their antiprotozoal activities. Characterizations of the drugs' formulations were accomplished utilizing Fourier-transform infrared spectroscopy, efficiency of drug entrapment, polydispersity index, zeta potential, size, and surface morphology. The nanoconjugates were tested against human cells to determine their toxicity in vitro. The majority of drug nanoconjugates exhibited amoebicidal effects against B. mandrillaris and N. fowleri. Amphotericin B-, Sulfamethoxazole-, Metronidazole-based nanoconjugates are of interest since they exhibited significant amoebicidal effects against both parasites (p < 0.05). Furthermore, Sulfamethoxazole and Naproxen significantly diminished host cell death caused by B. mandrillaris by up to 70% (p < 0.05), while Amphotericin B-, Sulfamethoxazole-, Metronidazole-based drug nanoconjugates showed the highest reduction in host cell death caused by N. fowleri by up to 80%. When tested alone, all of the drug nanoconjugates tested in this study showed limited toxic effects against human cells in vitro (less than 20%). Although these are promising findings, prospective work is warranted to comprehend the mechanistic details of nanoconjugates versus amoebae as well as their in vivo testing, to develop antimicrobials against the devastating infections caused by these parasites.
曼氏巴尔通体和福氏耐格里阿米巴原虫是能够引起致命感染的原生动物病原体。尽管死亡率超过 90%，但目前尚无有效的治疗方法。治疗仍然存在问题，涉及到重新利用药物，如唑类、两性霉素 B 和米替福新，但需要早期诊断。除了药物发现外，使用纳米技术修饰现有药物为开发针对这些寄生虫感染的治疗干预措施提供了希望。在此，开发了各种与纳米颗粒结合的药物，并评估了它们的抗原生动物活性。利用傅里叶变换红外光谱、药物包封效率、多分散指数、zeta 电位、粒径和表面形态对药物配方进行了表征。测试了纳米复合物对人细胞的毒性，以确定其体外毒性。大多数药物纳米复合物对曼氏巴尔通体和福氏耐格里阿米巴原虫均具有杀阿米巴作用。两性霉素 B、磺胺甲恶唑和甲硝唑为基础的纳米复合物具有重要的杀阿米巴作用，对两种寄生虫均具有显著的杀阿米巴作用（p < 0.05）。此外，磺胺甲恶唑和萘普生可使曼氏巴尔通体引起的宿主细胞死亡减少高达 70%（p < 0.05），而两性霉素 B、磺胺甲恶唑和甲硝唑为基础的药物纳米复合物使福氏耐格里阿米巴原虫引起的宿主细胞死亡减少高达 80%。单独测试时，本研究中测试的所有药物纳米复合物在体外对人细胞的毒性作用有限（小于 20%）。尽管这些是有希望的发现，但需要进一步的研究来理解纳米复合物与阿米巴之间的机制细节，以及它们的体内测试，以开发针对这些寄生虫引起的破坏性感染的抗菌药物。
